How do stressful experiences that happen in early life have such powerful direct effects on poor health decades later? When and how do these experiences become biologically embedded? To address this question, we are following a 1994-95 birth cohort of 2,232 twins (the E-Risk Study). The cohort is well- characterized, environmentally and phenotypically, with assessments at birth, 2,5,7,10,12, and 18 years, and has a dedicated biobank. Our research focuses on exposure to violence, one of the most common and severe sources of human stress. We begin by compiling cumulative dossiers of violence exposure in childhood and adolescence, including child maltreatment, sexual abuse, domestic violence, peer victimization, dating violence, and conventional crime. We then test the hypothesis that young people who are exposed to violence in childhood and adolescence will, by young adulthood, show compromised neuropsychological functioning, telomere erosion, and differential expression and epigenetic regulation of genes involved in the coordination of the stress response and the regulation of immune and inflammatory reactions. A key need in this research is for violence exposure to be disentangled from associated risk factors, including poverty, parents' mental health, and genetic liability. Analyses with the E-Risk cohort will isolat these effects of violence exposure by (a) comparing twins who are discordant for violence exposure on their psychobiological outcomes, (b) studying within-individual changes in psychobiological outcomes, using each child as his or her own control, and ultimately (c) identifying protective factors that mitigate biological embedding of exposure to violence. The E- Risk Study will be the first major developmental-longitudinal cohort study to bring together detailed assessments of multiple kinds of exposure to violence and multiple stress biomarkers, in order to characterize the mechanisms through which violence-exposed children may acquire lasting vulnerability to disease.